Protect Effects Of ER Stress Preconditioning On Neurons In Hippocampal Area Of The Rats With Status Epilepticus

Objective: To investigate the neuronal damage and the expressions of GRP78,XBP-1 in hippocampal areas of the rats with status epilepticus (SE) which were preconditioned by 2-Deoxyglucose(2-DG) induced endoplasmic reticulum stress(ERS), so as to evaluate the protect effects of ERS preconditioning on hippocampal neurons and the possible mechanism。Methods: The preconditioning group was administered 2-DG intraperitoneally with a dose of 150mg/kg body weight, once daily for 7 consecutive days. 24 hours following the last 2-DG dose, the lithium pilocarpine induced epilepsy model was established on both preconditioning group and SE group. Nissl staining was utilized to qualified the hippocampal neuronal damage at the 7th day after seizure. The expressions of GRP78 and XBP-1 in rats hippocampal areas were detected by immunochemistrical staining at six time points (before seizure, 6h, 12h, 1d, 2d and 7d after seizure).Results: 1. There were 25 rats in SE group and 22 rats in preconditioning group developed to SE. No detectable behavioral changes in normal group. The latency of SE in preconditioning group was longer than that in SE group (p＜0.05).2. In both SE group and preconditioning group neuronal damage could be seen in all hippocampal regions, which were more obvious in CA1 region according to the Nissl staining results. The number of survival neurons in SE group was much less than that of preconditioning group (p＜0.05). There was no significant hippocampal neuronal damage in normal group.3. Immunochemistrial staining results illustrated that in SE group the expressions of GRP78 and XBP-1 at 6h after seizure were above the normal level (p＜0.05), then kept increasing at the time points of 12h and 24h after seizure (p＜0.05)until the peak point of 2d(p＜0.05), and went back to normal level at the time point of 7d. The expressions of the two proteins in preconditioning group were above the normal level before SE (p＜0.05), and kept increasing at 6h and 12h after seizure (p＜0.05), then maintained at the highest level at 24h and 2d after seizure (p＜0.05) except the 2d's XBP-1 gray value going down, and went back to normal level at 7d. The expressions of GRP78 and XBP-1 in preconditioning group were stronger than those of SE group at the previous 4 time points (before seizure, 6h,12h,24h after seizure) (p＜0.05), while indifferential to that of SE group at the time points of 2d and 7d (P＞0.05) except the 2d' XBP-1 gray value being lower than that of SE group (p＜0.05). The hippocampal areas of rats in normal group also show positive expressions of GRP78 and XBP-1, the intensity of which were weaker than in SE group and preconditioning group (p＜0.05), and have no significant changes through the time course.Conclusion:1. 2-DG pretreatment could induce ERS preconditioning.2. 2-DG pretreatment could relieve the epileptogenesis of pilocarpine.3. Endoplasmic reticulum stress preconditioning could protect hippocampal neurons from damage in rats with status epilepticus.4. The XBP-1-GRP78 signal pathway may be an important mechanism in protective effects of ERS preconditioning on hippocampal neurons.